Neurodegenerative Changes in Aging and Dementia: A Comparison of Alzheimer and Lewy Body Type Pathology

Abstract

Whereas cortical senile plaques are evident in the vast majority of elderly people and as such can be considered part of the “normal” aging process, Lewy bodies are found in the cortex of a very small proportion (<5%) of normal aged (over 70 yr) individuals and may be more specifically disease-associated. Lewy bodies invariably appear in the cortex of elderly patients suffering from a form of dementia that is clinically distinct from Alzheimer’s disease (AD)—Senile Dementia of Lewy Body Type (SDLT). SDLT is part of the spectrum of Lewy body disease (which also includes diffuse Lewy body disease) and is distinguished by the relatively high incidence of mainly visual hallucinations. Although memory impairment (the cardinal feature of AD, also evident in SDLT) may to some degree be an inevitable concomitant of the aging process, hallucinations are not generally associated with normal aging and presumably relate in SDLT to specific disease-related alterations in brain function. At the histological level there is, however, no obvious correlation between the distribution or density of cortical Lewy bodies and the incidence of hallucinations, although at the biochemical level an interesting relationship is apparent. Distinct profiles of cholinergic and monoaminergic transmitter activities were evident in AD and SDLT, particularly with respect to the occurrence of hallucinations in the latter. Thus the presynaptic cholinergic enzyme choline acetyltransferase was significantly lower, whereas pre- and post-synaptic serotonergic activities (5HIAA and 5HT2 receptor binding) were relatively spared in the hallucinating SDLT group compared to AD and the non-hallucinating SDLT group. The concept of an imbalance between serotonin and acetylcholine with relatively hyperactive serotonergic and hypoactive cholinergic activities being associated with hallucinating experiences is consistent with the psychopharmacology of drugs affecting the respective systems. Thus, cholinergic antagonists and selective serotonergic agonists tend to be hallucinogenic, although whether cholinergic agonist or serotonergic (S2) antagonist drug treatments would alleviate hallucinations in SDLT remains to be determined.KeywordsLewy BodyNicotinic ReceptorCholine AcetyltransferaseSenile DementiaLewy Body DiseaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.